Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (B). Efficiency of pharmacological action

作者:Dzmitruk Volha; Szulc Aleksandra; Shcharbin Dzmitry; Janaszewska Anna; Shcharbina Natallia; Lazniewska Joanna; Novopashina Darya; Buyanova Marina; Ionov Maksim*; Klajnert Maculewicz Barbara; Gomez Ramirez Rafael; Mignani Serge; Majoral Jean Pierre; Angeles Munoz Fernandez Maria; Bryszewska Maria
来源:International Journal of Pharmaceutics, 2015, 485(1-2): 288-294.
DOI:10.1016/j.ijpharm.2015.03.034

摘要

This paper examines a perspective to use newly engineered nanomaterials as effective and safe carriers for gene therapy of cancer. Three different groups of cationic dendrimers (PAMAM, phosphorus, and carbosilane) were complexed with anticancer siRNA and the biophysical properties of the dendriplexes created were analyzed. The potential of the dendrimers as nanocarriers for anticancer Bcl-xl, Bc1-2, Mcl-1 siRNAs and additionally a scrambled sequence siRNA has been explored. Dendrimer/siRNA complexes were characterised by various methods including fluorescence, zeta potential, dynamic light scattering, circular dichroism, gel electrophoresis and transmission electron microscopy. In this part of study, the transfection of complexes in HeLa and HL-60 cells was analyzed using both single apoptotic siRNAs and a mixture (cocktail) of them. Cocktails were more effective than single siRNAs, allowing one to decrease siRNAs concentration in treating cells. The dendrimers were compared as siRNA carriers, the most effective being the phosphorus-based ones. However, they were also the most cytotoxic on their own, so that in this regard the application of all dendrimers in anticancer therapy will be discussed.

  • 出版日期2015-5-15